This proposal requests continued support for the MIT/Harvard Center for Magnetic Resonance (CMR) located at the Francis Bitter Magnet Laboratory, MIT, a joint effort between MIT and Harvard Medical School. During the coming five-year period we plan significant upgrades of existing equipment, acquisition of new instrumentation, and research initiatives in several new areas. Specifically, the P41 grant will continue to support an exciting core research program in magnetic resonance based structural biology focused on studies of membrane proteins, translation initiation, amyloid, new high frequency microwave technology for magnetic, methods for non-uniform sampling and dynamic nuclear polarization, and high temperature superconducting magnets for NMR. In addition, we will be developing new instrumentation as follows: (1) T-locks for the solution 750 and 900 MHz spectrometers; (2) upgrading of a 460 GHz/700 MHz dynamic nuclear polarization (DNP)/NMR spectrometer; (3) design and construction of helium recirculation system for low temperature DNP experiments in the 10- 60 K regime; (4) design and construction of a new generation of MAS probes that are balanced on all channels; (5) design and construction of the next generation of NMR console on a chip. The research of the five TR&D's will implement new technology for NUS, for preparation and analysis of membrane protein structures, studies of sedimented samples, high frequency MAS for membrane and amyloid protein, improving resolution at low temperatures and 17-0 labeling and spectroscopy.